Thromboembolism is a condition in which the blood has become solidified within the heart or a blood vessel. When the blood is stopped by a thromboembolism, a lesion develops in the area nourished by that blood vessel. An antithrombotic agent is necessary to prevent thromboembolism because a thromboembolism can be fatal.
As regards the assessment of the efficacy of antithrombotic agents and antiplatelet agents, it is inherently difficult to assess the efficacy of an antiplatelet agent owing to the presence of a strong platelet agonist called thrombin in the blood. There is in fact no effective means of assessment.
The potentiation of platelet activity was considered as a cause of thromboembolism, but there are no data to be found that clearly show clot formation to be speeded up when platelet activity is abnormally accelerated. From this viewpoint, there are data on the measurement of the degree of clot formation obtained using a thromboelastograph by adding adenosine diphosphate (ADP (final concentration 8.3 μM)) or collagen (Col: final concentration 10 μg/mL), which are platelet agonists, to whole blood (Non-patent Reference 1). The results are shown in Table 1. The control in Table 1 means blood itself without ADP, collagen, or the like added. The data in Table 1 are stated as the mean±standard deviation. R and K are thromboelastograph parameters. R is the time it takes for fibrin to be formed. K is the time it takes a clot to be formed.
TABLE 1RKR + KM AADPcontrol5.9 ± 1.72.4 ± 0.48.3 ± 1.958.5 ± 1.88.3 μM/L5.0 ± 1.03.1 ± 0.68.1 ± 1.657.9 ± 2.6Col.control6.4 ± 2.62.6 ± 0.69.0 ± 2.957.3 ± 3.610 μg/mL5.3 ± 1.42.5 ± 0.57.8 ± 1.557.9 ± 3.9
The results in Table 1 indicate that R shortens significantly when ADP or collagen is added, but that K lengthens significantly when ADP is added, and shows no significant difference when collagen is added, and that R+K shows no significant difference when ADP is added, and shortens significantly when collagen is added. Therefore, clot formation speeds up when platelet aggregation is stimulated by collagen, and fibrin formation speeds up but clot formation slows down when platelet aggregation is stimulated by ADP, and no difference in clot formation is shown as a result. The amounts of platelet agonists such as adenosine diphosphate and collagen added in Table 1 are twice or more the maximum clinical doses to induce platelet activity. This amount is the amount that usually immediately coagulates the entire quantity of platelets. Despite this, the results in Table 1 simultaneously show that even addition of a concentration of platelet agonist twice or more the maximum clinical dose to induce platelet activity causes only slight acceleration of clot formation or causes no clear acceleration of clot formation.
The reason for this is believed to be that the thrombin present in the blood is itself an extremely potent platelet agonist and inhibits the effects of the other platelet agonists ADP and collagen. In Non-patent Reference 2, an antithrombin agent (heparin or argatroban) is added to slightly weaken the power of the thrombin in the blood. The platelets are then stimulated by adding ADP or collagen in the same final concentrations as in Table 1, and the extent of clot formation is measured on the thromboelastograph. The measurement results are shown in Table 2.
TABLE 2RKA N Gcontrol9.6 ± 3.72.8 ± 0.872.7 ± 5.8 Hep(0.1 U/mL)26.4 ± 10.611.4 ± 6.2 39.1 ± 13.9Hep + Col(10 μg/mL)19.2 ± 7.1 8.5 ± 4.645.4 ± 13.3Hep + ADP(8.3 μM/L)16.8 ± 8.1 7.4 ± 3.543.7 ± 13.2control7.6 ± 2.42.2 ± 0.776.8 ± 3.7 ARG(0.3 μg/mL)29.8 ± 11.59.8 ± 5.144.5 ± 14.6ARG + Col(10 μg/mL)21.6 ± 5.6 6.3 ± 2.452.5 ± 10.8ARG + ADP(8.3 μM/L)20.6 ± 2.9 6.2 ± 1.753.3 ± 9.1 
R and K lengthen when heparin or argatroban is added, and R and K clearly shorten when a platelet activator (ADP or collagen) is added. ANG, which represents the rapidity of clot formation, appears to tend to be increased by the platelet activators. This result clearly shows that the acceleration of platelet aggregation by the addition of the antithrombin agent heparin or argatroban can accelerate clot formation.    Non-patent Reference 1: American Society of Anesthesiologists (ASA) meeting abstract A-534 2002    Non-patent Reference 2: American Society of Anesthesiologists (ASA) meeting abstract A-1 62 2003